At some point, everyone has experienced a temporary groggy feeling after waking up called sleep inertia. Scientists know a lot about sleep inertia already, including how it impairs cognitive and motor abilities, and how it varies with the time of day and type of sleep that precedes it. They even have pictures of how the brain wakes up piece by piece.
People with idiopathic hypersomnia or IH display something that seems stronger, termed “sleep drunkenness,” which can last for hours. Czech neurologist Bedrich Roth, the first to identify IH as something separate from other sleep disorders, proposed sleep drunkenness as IH’s defining characteristic.
Note: Emory readers may recall the young Atlanta lawyer treated for IH by David Rye, Kathy Parker and colleagues several years ago. Our post today is part of IH Awareness Week® 2017.
Sleep drunkenness is what makes IH distinctive in comparison to narcolepsy, especially narcolepsy with cataplexy, whose sufferers tend to fall asleep quickly. Those with full body cataplexy can collapse on the floor in response to emotions such as surprise or amusement. In contrast, people with IH tend not to doze off so suddenly, but they do identify with the statement “Waking up is the hardest thing I do all day.”
At Emory, neurologist Lynn Marie Trotti and colleagues are in the middle of a brain imaging study looking at sleep drunkenness.
“We want to find out if sleep drunkenness in IH is the same as what happens to healthy people with sleep inertia and is more pronounced, or whether it’s something different,” Trotti says. Read more
Anesthesiologist Paul Garcia and his colleagues are presenting two posters at the Society of Neuroscience meeting this week, whose findings may raise concerns about two non-stimulant drugs Emory sleep specialists have studied for the treatment of hypersomnia: flumazenil and clarithromycin.
For both, the data is in vitro only, so caution is in order and more investigation may be needed.
With flumazenil, Garcia and colleagues found that when neurons are exposed to a low dose for 24 hours, the cells increase expression of some GABA receptor forms.
This could be part of a mechanism for tolerance. I heard some anecdotes describing how flumazenil’s wake-promoting effects wear off over time at the Hypersomnia Foundation conference in July, but it’s not clear how common the phenomenon is.
Flumazenil’s utility in hypersomnia became known after the pioneering experience of Anna Sumner, who has reported being able to use the medicine for years. See this 2013 story in Emory Medicine. Read more
A visitor might not realize this was a meeting devoted to people who experience excessive daytime sleepiness. The 2015 Hypersomnia Foundation Conference on Saturday was full of energy, with:
*more than 245 attendees, about twice as many people as last year’s conference
*medical experts from France, Wisconsin and Louisiana — in addition to Emory
*data from several recent clinical trials
*some signs of industry interest in hypersomnia
Hypersomnia is a sleep disorder in which individuals feel frequent or constant sleepiness and need to sleep for long portions of the day (more than 70 hours per week). It is distinct from other sleep disorders such as narcolepsy and sleep apnea, but its prevalence is still unclear. Conventional stimulants such as amphetamine or modafinil often can be used to treat the sleepiness, but some with hypersomnia find these drugs ineffective or hard to tolerate.
Previous research at Emory has shown that many individuals with hypersomnia have a substance in their spinal fluid that acts like a sleeping pill, enhancing the action of the neurotransmitter GABA. The identity of this mysterious substance is unknown, but Emory researchers report that they are close to identifying it. That could give hypersomnia a “molecular handle” similar to what narcolepsy has, with loss of hypocretin-producing neurons.
The terminology is still up in the air — keynote speaker Isabelle Arnulf from Paris said, “The term ‘idiopathic hypersomnia’ does not mean that you are an idiot.” Rather, she said, it means that even specialists can have trouble distinguishing hypersomnia from other sleep disorders, and “idiopathic” signifies that the detailed cause is still under investigation.
From Emory Medicine, Spring 2013
A small clinical study of clarithromycin for the sleep disorder hypersomnia shows that the antibiotic can combat patients’ subjective experience of sleepiness, but it does not seem to improve reaction time measured in a video-game-type vigilance task.
The effects of clarithromycin in hypersomnia were first observed by Emory doctors when a pioneering patient (Anna Sumner, whose story is told in this Emory Medicine article) unexpectedly experienced sleeplessness when taking it for a respiratory infection.
The results of the study were published online by Annals of Neurology on June 10.
Lynn Marie Trotti, MD, David Rye, MD, PhD and colleagues from the Department of Neurology and Emory Sleep Center conducted the study, which involved 23 patients.
Advantages of clarithromycin:
- It’s inexpensive and widely available.
- It’s an option for people dealing with hypersomnia for whom other medications, such as modafinil, are not helpful or tolerable.
- It represents an alternative to flumazenil, the benzodiazepine antidote that has been shown to help some hypersomnia patients. Flumazenil used to be very scarce, and shortages occur (Hypersomnia Foundation/American Society of Health System Pharmacists).
Disadvantages of clarithromycin:
- It’s an antibiotic, so it probably changes intestinal bacteria.
- Chronic use could promote the growth of antibiotic-resistant bacteria.
- Most patients reported an altered sense of taste or smell. Some describe this as a metallic mouth sensation.